Propionic acid derivatives

ibuprofen(common trade name, brufen)

Is a widely used and available drug

Has all the pharmacological actions ,anti-
inflammatory,analgesic and antipyretic action
It is 99% protein bound
Doses of 2400mg are equivalent to 4gm of aspirin
Its metabolised by CYP2C8 and CYP2C9 in the
liver
Use of ibuprofen and aspirin may decrease total
anti inflammatory effect
Has a slower onset of action than paracetamol
but a longer duration of action
 Propionic acids
Are aryl propionic acid derivatives
Have many benefits over aspirin and
indomethacine
All have class characteristics and effects
Examples
Ibuprofen,naproxen,fenoprofen,ketoprofen
Flubiprofen and oxaprozin
 indications
Symptomatic treatment of rheumatoid
arthritis
Osteoarthritis
Ankylosing spondylitis
Acute gouty arthritis
Dymenorrhea
All their clinical actions are comparable to
aspirin
Ibuprofen was the first in this class so
greater experience exists
Naproxyn has a long half life and is given
twice daily
Other members that are in various stages of
development
include,fenbufen,carprofen.indobufen,tiaprof
enic acid
 Pharmacological properties
 All have same characteristics
 All are COX inhibitors
 Potency differs from one to another
 Naproxen is 20 times more active than aspirin
 Ibuprofen,fenoprofen and aspirin have same
potency
 All have anti-platelet activity and thus prolong
bleeding time
 Naproxen has a significant anti-leukocyte activity
 Naproxen is better tolerated than others in this
class
 Drug interactions
Mainly a result of high protein binding

They do not alter effect of oral hypoglycemic

or warfarin

However care needs to be taken with patients

on warfarin because of their Antiplatelets
action
They may also cause gastrointestinal lesions
 dose
Ibuprofen-----400 to 800mg ,3 to 4 times a day
Naproxen-----250mg to 500mg twice daily
Ketoprofen--------50-75mg two to four times
daily
 Propionic acid derivatives
ibuprofen(common trade name, brufen)

Is a widely used and available drug

Has all the pharmacological actions ,anti-
inflammatory,analgesic and antipyretic action
It is 99% protein bound
Doses of 2400mg are equivalent to 4gm of aspirin
Its metabolised by CYP2C8 and CYP2C9 in the
liver
Use of ibuprofen and aspirin may decrease total
anti inflammatory effect
Has a slower onset of action than paracetamol
but a longer duration of action
 pharmacology

Molecular wt 206.20,pka-4.43
Mechanism of action-inhibition of
cyclooxygenase
Onset of action -30minutes,duration of action
4 to 6hrs
 Actions/indications

Pain and inflammation in rheumatic disease

and other musculoskeletal disorders
Mild to moderate pain, in dysmenorrhea,post
operative analgesia
Migraine
Dental pain
Fever
Post immunization pyrexia
 Pharmacokinetics and metabolism

Rapid,99% protein bound

Time to peak concentration in plasma is 15 t0 30
mins
Half life in plasma is 2 hours
It passes in synovial space and can cross the
placenta
Excretion is complete and rapid with 90% of
ingested dose excreted in urine as metabolites or
conjugates
Major metabolite is hydroxylated or carboxylated
compound
distribution
 metabolism

Mainly hepatic,elimination ,1.8 to 2 hrs,

elimination
 precautions

Cross sensitivity to other Nsaids

May cause brochoconstriction or anaphylaxis
In pregnancy,especialy second half is not
recommended, may cause adverse effects on
the fetus(premature closure of Ductus
arteriosus
In breast feeding-normal doses safe
In pediatrics –safe
Geriatrics-care is needed because they are
more susceptible to age related complications
 Side effects

G.I side effects

Epigastric pain
Nausea
Sensation of fulness
Thrombocytopenia
Skin rash
Headache
Dizziness
Blurred vision
Drug interactions
 contraindications

Patients with
 nasal polyps,
Angioedema
Bronchospasms,especially those reactive to
aspirin
Peptic and duodenal ulcers
 Patient monitoring

Blood urea and nitrogen(BUN),creatinine or

potassium levels in serum-should be done in
patients at risk of hepatic or renal disease
Hematocrit and hemoglobin levels
Stool tests
Liver function tests
Routine monitoring not essential unless at
risk
Patient consultation
 dose

Adults and children over 12yrs-initially,300-

400mg,3 to 4times daily,max
24oomg,maitenance 0.6gm-1.2gms
For rheumatoid arthritis doses up to 3.2 gms
may be used
Child 1-3months-
3-6month-over 5kg body weight,-
50mgs ,3times daily,max 30mg/kg in 3 or 4
divided doses
Other doses –refer to formulary and notes
 Preparations available

Sugar coated tablets containing 200,400 and

600mg ibuprofen

For children liquid preparations exist

Ibuprofen is a derivative of phenylpropionic acid.
In doses of 2.4 g daily it is is equivalent to 4 g
of Aspirin in anti-inflammatory effect. Oral ibuprofen is
often prescribed in lower doses (< 2.4 g/d), at which
it has analgesic but not antiinflammatory efficacy.
It is available in low dose forms under several trade
names (e. g. Nurofen® – film-tabl. 400 mg). A topical
cream preparation is absorbed into fascia and muscle.
A liquid gel preparation of ibuprofen provides
prompt relief in postsurgical dental pain. In comparison
with indometacin, ibuprofen decreases urine
output less and also causes less fluid retention. It is
effective in closing ductus arteriosus in preterm infants,
with much the same efficacy as indometacin.
Chemical structures of the propionic acid
derivatives (propionates)
Flurbiprofen is a propionic acid derivative with a
possibly more complex mechanism of action than
other NSAIDs. Its (S)(-) enantiomer inhibits COX
nonselectively, but it has been shown in rat tissue to
also affect TNF-α and NO synthesis. Hepatic
metabolism is extensive. It does demonstrate
enterohepatic circulation. The efficacy of
flurbiprofen at dosages of 200–400 mg/d is compa-
rable to that of Aspirin and other NSAIDs for patients
with rheumatoid arthritis, ankylosing spondylitis,
gout, and osteoarthritis. Flurbiprofen i.v. is effective
for perioperative analgesia in minor ear, neck, and
nose surgery and in lozenge form for sore throat.
Its adverse effect profile is similar to other NSAIDs.
Ketoprofen is a propionic acid derivative that
inhibits both COX (nonselectively) and lipoxygenase.
Concurrent administration of probenecid elevates
ketoprofen levels and prolongs its plasma half-life.
The effectiveness of ketoprofen at dosages of
100–300 mg/d is equivalent to that of other NSAIDs
in the treatment of rheumatoid arthritis, osteoarthritis,
gout, dysmenorrhea, and other painful conditions.
In spite of its dual effect on prostaglandins and
leukotrienes, ketoprofen is not superior to other
NSAIDs. Its major adverse effects are on the GIT
and the CNS.
Phenylbutazone is a derivative of pyrazolidinedione
with a high GI toxicity. It is rarely used now.